Activity of Plasma Membrane V-ATPases Is Critical for the Invasion of MDA-MB231 Breast Cancer Cells

Cotter, Kristina; Capecci, Joseph; Souad, Sennoune; Huss, Markus; Maier, Martin A.; Martı́nez-Zaguilán, Raul; Forgac, Michael

doi:10.1074/jbc.m114.611210

Cited by 98 publications

(120 citation statements)

References 56 publications

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“…35 The upregulation of isoleucine reduced the biotin concentration and the irritating effects of hydroxyisovalerate, leading to plasma membrane shrinkage. 36 Therefore, nanomaterialinduced plasmolysis likely reflects an increase in isoleucine, as shown in Figure 8c. The mechanisms underlying the increase in Figure 8.…”

Section: ■ Discussionmentioning

confidence: 96%

Envelopment–Internalization Synergistic Effects and Metabolic Mechanisms of Graphene Oxide on Single-Cell Chlorella vulgaris Are Dependent on the Nanomaterial Particle Size

Ouyang

Zhou

2015

ACS Appl. Mater. Interfaces

129

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The interactions between nanomaterials and cells are fundamental in biological responses to nanomaterials. However, the size-dependent synergistic effects of envelopment and internalization as well as the metabolic mechanisms of nanomaterials have remained unknown. The nanomaterials tested here were larger graphene oxide nanosheets (GONS) and small graphene oxide quantum dots (GOQD). GONS intensively entrapped single-celled Chlorella vulgaris, and envelopment by GONS reduced the cell permeability. In contrast, GOQD-induced remarkable shrinkage of the plasma membrane and then enhanced cell permeability through strong internalization effects such as plasmolysis, uptake of nanomaterials, an oxidative stress increase, and inhibition of cell division and chlorophyll biosynthesis. Metabolomics analysis showed that amino acid metabolism was sensitive to nanomaterial exposure. Shrinkage of the plasma membrane is proposed to be linked to increases in the isoleucine levels. The inhibition of cell division and chlorophyll a biosynthesis was associated with decreases in aspartic acid and serine, the precursors of chlorophyll a. The increases in mitochondrial membrane potential loss and oxidative stress were correlated with an increase in linolenic acid. The above metabolites can be used as indicators of the corresponding biological responses. These results enhance our systemic understanding of the size-dependent biological effects of nanomaterials.

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Section: ■ Discussionmentioning

confidence: 96%

Envelopment–Internalization Synergistic Effects and Metabolic Mechanisms of Graphene Oxide on Single-Cell Chlorella vulgaris Are Dependent on the Nanomaterial Particle Size

Ouyang

Zhou

2015

ACS Appl. Mater. Interfaces

129

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“…Increased cancer cell invasive activity is frequently associated with aberrant V‐ATPase plasma membrane localization suggesting that increased acidification of the extracellular space plays an important role 29, 33, 34, 37, 47, 48, 49, 50, 51, 52…”

Section: V‐atpase Function In Cancer Cellsmentioning

confidence: 99%

“…To investigate whether plasma membrane or intracellular V‐ATPases were responsible for the invasive phenotype of breast cancer cells, Cotter et al inhibited plasma membrane V‐ATPase activity in MDA‐MB‐231 cells with a monoclonal antibody to the V5 epitope of a V5 tagged V o c subunit construct (which, in contrast to pharmacological inhibitors or RNAi‐mediated subunit ablation, would be expected to specifically target plasma membrane localized V‐ATPase) and found that specific inhibition significantly decreased in vitro invasion 49. Other studies of breast cancer cells have also linked V‐ATPase subunit expression to invasion.…”

Section: V‐atpase Function In Cancer Cellsmentioning

confidence: 99%

Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer

et al. 2018

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Vacuolar ATPase (V‐ATPase) is an ATP‐dependent H+‐transporter that pumps protons across intracellular and plasma membranes. It consists of a large multi‐subunit protein complex and influences a wide range of cellular processes. This review focuses on emerging evidence for the roles for V‐ATPase in cancer. This includes how V‐ATPase dysregulation contributes to cancer growth, metastasis, invasion and proliferation, and the potential link between V‐ATPase and the development of drug resistance.

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“…V-ATPase is considered to induce tumor invasion and multi-drug resistance in several malignant tumors, due to its contribution in maintaining the pH i under an acidic microenvironment by inducing proton extrusion into the extracellular medium (12,15). The plasma membrane V-ATPase is critical for the invasion and migration of MDA-MB-231 breast cancer cells in vitro (37). V-ATPase expression was elevated in the ellipticine-resistant UKF-NB-4ELLI cell line and mediated its ellipticine resistance via the sequestration of ellipticine into the subcellular compartments (38).…”

Section: Discussionmentioning

confidence: 99%

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

et al. 2018

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Abstract. Vacuolar H + -ATPase (V-ATPase) serves a key role in adjusting and maintaining the intracellular pH, as well as in regulating the drug resistance of tumor cells. In recent years, the expression level of V-ATPase has been considered to be able to predict the sensitivity of breast cancer cells to chemotherapy drugs. Cluster of differentiation 147 (CD147) is known to serve a key role in the development and progression of breast cancer. The present study aimed to identify the role CD147 and V-ATPase in chemoresistance in breast cancer, and to characterize the regulation of CD147 on V-ATPase. Firstly, the expression levels of CD147 and V-ATPase were detected in chemotherapy-resistance breast cancer samples. It was demonstrated that V-ATPase was highly expressed in chemotherapy-resistance breast cancer samples, and that its expression was correlated with CD147 expression. Subsequently, MCF-7 and MDA-MB-231 cells were used to study the regulatory effect of CD147 on the expression and function of V-ATPase. Gene transfection or small interfering RNA transfection were used to control the expression of CD147 in the two cell lines. The results revealed that the overexpression of CD147 increased the expression of V-ATPase in MCF-7 cells, whereas CD147 knockdown decreased V-ATPase expression in MDA-MB-231 cells. It was also observed that CD147 affected the V-ATPase activity, regulating the transmembrane pH gradient of cancer cells. These results demonstrated that CD147 was associated with the sensitivity of chemotherapeutic drugs of epirubicin and docetaxel, while pantoprazole was able to partially reverse the CD147-mediated chemoresistance in breast cancer. Therefore, the current study provided a possible mechanism for further examination of drug resistance in breast cancer.

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Activity of Plasma Membrane V-ATPases Is Critical for the Invasion of MDA-MB231 Breast Cancer Cells

Cited by 98 publications

References 56 publications

Envelopment–Internalization Synergistic Effects and Metabolic Mechanisms of Graphene Oxide on Single-Cell Chlorella vulgaris Are Dependent on the Nanomaterial Particle Size

Envelopment–Internalization Synergistic Effects and Metabolic Mechanisms of Graphene Oxide on Single-Cell Chlorella vulgaris Are Dependent on the Nanomaterial Particle Size

Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

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